Fig. 2: Crystal structures of nanobody-RBD complexes.

a The four nanobodies of this study are shown in cartoon and labelled. The figure was generated by superimposing the RBD protein from each crystal structure, only one RBD monomer is shown. Also shown is ACE2 (cyan surface) from the RBD ACE2 complex (PDB 6M0J), positioned by superposition of the RBD. Nanobodies C5 and H3 compete with ACE2 for binding to RBD. F2 and C1 bind to a different epitope, although a loop of C1 (G42) would clash with ACE2 (arrow). b RBD is shown as a surface, the RBD molecule has been rotated by 90° relative to a. The surface is coloured magenta corresponds to the epitope engaged by both C1 and F2, in red is the additional region recognised by C1 only. In yellow is the epitope recognised by C3 only, in black by H3 only and in green by both C5 and H3. c The same molecule and colour scheme as b but rotated by 90° to more clearly show the H3 and C5 epitopes. The key molecular interactions between d C5, e H3, f C1, and g F2 and RBD are identified and labelled. RBD is in approximately in the same orientation as a. In f and g coloured in magenta and gold respectively is the portion of RBD that is also recognised by both C1 and F2. h C1 and F2 bind to RBD in different orientations and overlap at residues 102 and 103. Their spatial relationship can be described as an approximate 40° rotation around the main chain at 102 and 103. i In the F2 (blue) RBD (cyan) complex, Y102 of F2 results in a displacement of the helix at Y369 of RDB relative to the C1 (red) and RBD (brown) complex. The orientation of the molecules are the same as shown in Fig. 2a. All structural figures were prepared using PyMOL (http://www.pymol.org/).